Allogeneic stem cell transplantation and targeted therapy for FLT3/ITD+ acute myeloid leukemia: an update

Abstract

Survival of patients with acute myelogenous leukemia (AML), particularly in younger patients, has improved in recent years due to improved understanding of disease biology, post remission therapies and supportive care. AML, however, remains difficult to treat as many patients will still ultimately relapse and die of their disease. This is particularly true in AML patients with identified FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) molecular mutations, which typically confers a poor prognosis. The FLT3-ITD mutation occurs in about one-quarter of patients diagnosed with AML. Oftentimes, these patients are referred for early allogeneic hematopoietic stem cell transplantation (HSCT) in hopes of overcoming this poor prognostic factor. Several studies have demonstrated some benefit with HSCT in patients with FLT3-ITD mutation. However, recent data suggested that FLT3-ITD mutation remains a poor prognostic factor even after early HSCT; these patients remain at risk for early relapse after transplantation, emphasizing ongoing efforts to explore maintenance therapy with FLT3-ITD inhibitors in the post-transplant setting.

Keywords::

• drug resistance
• FLT3 AML
• hematopoietic stem cell transplantation
• improving outcomes
• tyrosine kinase inhibitors

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The FMS-like tyrosine kinase 3-internal tandem duplications (FLT3-ITD) mutation occurs in about one quarter of patients diagnosed with acute myelogenous leukemia.

• Although complete remission rates are similar in patients with FLT3-ITD+ compared to those with FLT3-wild type with conventional chemotherapy, the risk of relapse has been markedly higher in FLT3-ITD+ patients when treated with chemotherapy alone.

• To attempt to overcome the poor prognostic factor of FLT3-ITD positivity, many patients are referred to early allogeneic hematopoietic stem cell transplantation in complete remission-1.

• However, outcome data after allogeneic hematopoietic stem cell transplantation in this patient population are limited, and there are to date no prospective trials that have evaluated the efficacy of this strategy.

• Recent data suggested that FLT3-ITD mutation remains a poor prognostic factor even after early hematopoietic stem cell transplantation.

• Current research efforts are looking at the strategies such as incorporation of FLT3 inhibitor, early titration of immunosuppression and pre-emptive administration of donor lymphocyte infusion in eligible patients to prevent relapses after allogeneic hematopoietic stem cell transplantation.